Determinations of the central neurotransmitter effects of ethanol are extremely valuable in the evaluation of the drug's mechanism of action. Whereas many studies on neurotransmitter changes in the whole brain during acute ethanol intoxication have been reported, a careful correlative study of the major neurotransmitters in various areas of the brain has not been carried out. Free neurotransmitter determinations are especially valuable because they suggest the amount of neurotransmitter available for use at the receptor during the drug's action. The present project will follow the changes in central levels of free acetylcholine, norepinephrine, serotonin, and dopamine in the cerebral cortex, reticular formation and cerebellum, three sites where ethanol is suggested to have its major action. The project is made possible by the relatively recent development of methods by which very small quantities of neurotransmitters may be quantitated, a selective application of combined gas chromatography/mass spectrometry known as mass fragmentography. Brain perfusates will be collected with cortical cups and push-pull cannulas in awake but immobilized rabbits, and from awake and freely-moving rats. Ethanol-induced central neurotransmitter changes will be correlated with blood ethanol, electroencephalographic tracings, blood pressure changes and behavioral intoxication in an attempt to determine the "neurotransmitter correlates" of ethanol intoxication. Such information will be valuable in deriving a theory for the mechanism of acute ethanol intoxication and possible antagonism of ethanol by centrally-acting autonomic drugs for social and toxicological purposes. BIBLIOGRAPHIC REFERENCES: Graham, D.T. and Erickson, C.K., "Alteration of ethanol-induced CNS depression: Ineffectiveness of drugs that modify cholinergic transmission". Psychopharmacologica 34: 173-180 (1974). Erickson, C.K. and Matchett, J.A. "A time-course study of spontaneous locomotor activity and central catecholamines in mice after ethanol". Fed. Proc. 34: 780 (1975).